Rib-X Reports Positive Top-Line Data from Phase 2b Study of Delafloxacin in Patients with Acute Bacterial Skin and Skin Structure Infections
—Delafloxacin Achieves Statistical Superiority Over Vancomycin in Primary Endpoint, Investigators' Global Assessment of Cure—
—Results Strongly Support Planned Initiation of Phase 3 Study in 2H2012—
NEW HAVEN, Conn.--(BUSINESS WIRE)--Dec 15, 2011 - Rib-X Pharmaceuticals, Inc., a biopharmaceutical company developing new antibiotics to provide superior coverage, safety and convenience for the treatment of serious and life-threatening infections, today announced positive top-line results from the Company's Phase 2b clinical trial of delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSI), including infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin met or exceeded primary and secondary efficacy endpoints evaluated to date in comparison to Zyvox® (linezolid), with and without aztreonam, and vancomycin, with and without aztreonam, including endpoints based on the draft guidance from the US Food and Drug Administration (FDA) in ABSSSI. Of note, for the primary endpoint of Investigators' Global Assessment of Cure, delafloxacin demonstrated statistical superiority in comparison to vancomycin (95% Confidence Interval -30.3%, -2.3%; p=0.031). Based on this top-line analysis and other data, the Company believes delafloxacin has demonstrated a level of efficacy that strongly supports the Company's planned initiation of a Phase 3 study of delafloxacin in the second half of 2012. Analyses of the full dataset are ongoing and Rib-X plans to present more detailed results at a future scientific meeting.
“It is rare for an antibiotic candidate to demonstrate statistical superiority in a clinical trial, let alone in a Phase 2b study,” said William D. O'Riordan, MD, FACEP, Medical Director, E Study Site and a lead investigator in the study. “Given delafloxacin's demonstrated broad spectrum of coverage, including MRSA, and IV-to-oral dosing regimens, I believe delafloxacin could be a much needed addition to the antibiotic treatment armamentarium. This is especially important for physicians in the emergency department who need empiric front-line treatments that not only offer a broad spectrum of coverage, but also offer ease of dosing, good tolerability and the potential for lower overall treatment costs, reduced hospital stays and improved patient outcomes.”
2b ABSSSI Top-Line Data Results
(300 mg BID) versus Zyvox (600 mg BID) and vancomycin (1,000 to
2,000 mg BID)
|Investigators' Global Assessment of Cure1|
|% Clinical Cure (ITT2)||70.4%||64.9%||54.1%|
(95% Confidence Interval -30.3%, -2.3%; p=0.031).
2ITT - Intent to Treat
|Global Assessment of Cure in Patients with Confirmed
|% Clinical Cure (MITT3)||59.3%||51.5%||56.3%|
|Objective Endpoint 48-72 hours4|
Cessation of Spread
of Erythema and
Absence of Fever at 48
Phase 2b Safety Results
Overall adverse event (AE) rates were statistically equivalent across the study for delafloxacin (74%), Zyvox (72%) and vancomycin (65%). The leading AE associated with delafloxacin was gastrointestinal (GI) disorder with mild to moderate diarrhea as the most common specific event. The leading AE for Zyvox was also GI disorder, with the most common specific event being nausea. The leading AE for vancomycin was disorders of the skin, with the most common specific event being pruritis (itching). In the Zyvox arm, two subjects experienced thrombocytopenia. In the vancomycin arm, three patients experienced renal issues, including two renal failures. Importantly, as observed in earlier Phase 2 studies, delafloxacin did not demonstrate evidence for the toxicities that have been common in the fluoroquinolone class of antibiotics, such as phototoxicity, dysglycemia and QT prolongation.
“Delafloxacin has consistently demonstrated its potential utility as a well-tolerated, broad spectrum antibiotic that effectively targets resistant pathogens across four Phase 2 clinical studies and more than 1,200 patients, including in this latest Phase 2b study, in which the patient population was extremely sick based on lesion size and the high rates of MRSA,” said Scott Hopkins, MD, Chief Medical Officer of Rib-X. “We accomplished our primary goal of reconfirming delafloxacin's efficacy and safety profile under both the traditional endpoints of global assessment and, now also, under the new objective endpoints issued by the FDA. Given that antibiotic clinical trials are designed as non-inferiority trials, demonstrating delafloxacin's superiority over vancomycin and strong performance against Zyvox is clinically very exciting and clearly supports initiation of Phase 3 studies of delafloxacin in ABSSSI.”
“We've successfully conducted what we believe is one of the most rigorously designed and comprehensive studies in the antibiotic space since the FDA issued their draft guidance on ABSSSI development in 2010,” said Mark Leuchtenberger, President and Chief Executive Officer of Rib-X. ”We believe the outstanding results from this study provide us with multiple options to optimize our Phase 3 trial design in this indication and look forward to working with the FDA and EMA on future clinical development plans.”
The Phase 2b study was a randomized, double-blind comparison of delafloxacin, Zyvox, with and without aztreonam, and vancomycin, with and without aztreonam, using objective efficacy measures to evaluate the relative clinical responses in subjects with ABSSSI; aztreonam was added by the investigator based on the believed or confirmed presence of Gram-negative bacteria. ABSSSI is an infection involving subcutaneous tissues or requiring surgical intervention, of one of the following four types: cellulitis/erysipelas, wound infection, major cutaneous abscess or burn infection. The trial enrolled a total of 256 subjects across multiple centers in the United States. Subjects were randomized into three treatment arms to receive either delafloxacin, 300 mg intravenously every 12 hours, or the recommended dosing for Zyvox, both with and without aztreonam, or vancomycin, both with and without aztreonam. The primary endpoint for the study was the Investigators' Global Assessment of Cure. Additionally, a key goal was to assess the utility, variability and measurement techniques of several objective measures of clinical efficacy for use in future clinical trials. Efficacy was evaluated at multiple time points during the study, with a focus on the first five days of administration, through assessments of objective signs and symptoms of infection such as the extent/size of infection, fever, measurement of biochemical markers of inflammation and culture and susceptibility testing of bacterial isolates.
Delafloxacin, a novel antibiotic candidate of the fluoroquinolone class, is intended for use as an effective and convenient first-line therapy primarily in hospitals prior to the availability of a specific diagnosis. Unlike currently available first-line treatments, delafloxacin has the potential to offer broad spectrum coverage as a monotherapy, including for methicillin-resistant Staphylococcus aureus (MRSA), with both intravenous and oral formulations. Delafloxacin has successfully completed four Phase 2 clinical studies and has been studied in over 1,200 subjects to date.
Rib-X Pharmaceuticals, Inc. is a biopharmaceutical company developing new antibiotics to provide superior coverage, safety and convenience for the treatment of serious and life-threatening infections. The Company's proprietary drug discovery platform provides an atomic-level, three-dimensional understanding of interactions between drug candidates and their bacterial targets and enables design of antibiotics with enhanced characteristics. Rib-X has two antibiotic candidates in clinical development. Delafloxacin is an enhanced spectrum IV/oral antibiotic intended for use as first-line monotherapy primarily in hospitals and recently completed a Phase 2b clinical trial for the treatment of acute bacterial skin and skin structure infections. Radezolid is a next-generation IV/oral oxazolidinone designed to be a potent antibiotic with a safety profile permitting long-term treatment of resistant infections. The Company's pipeline also includes its preclinical RX-04 program, partnered with Sanofi, S.A., and other discovery stage anti-infective programs.
Zyvox® is a registered trademark of Pfizer, Inc.
Contact: Rib-X Pharmaceuticals, Inc.
Bob Conerly, 203-624-5606
Sarah Cavanaugh, 781-235-3060
Kari Watson, 781-235-3060
Posted: December 2011